Prior to the present invention substituted purine compounds used in the method of the present invention have been taught in U.S. Pat. No. 4,199,574. The teachings of this reference are incorporated herein by reference thereto.
The compounds disclosed were reported to have antiviral activity against various classes of DNA and RNA viruses both in in vitro and in vivo experiments. In particular, the compounds were found to be active as anti-virals against cytomegalovirus, adenovirus, especially adenovirus 5, rhino virus, Mengo virus and Sindbis virus. They are also especially active as an antiviral against vaccinia, and herpes viruses, including simplex, zoster and varicella, in mammals, which cause such diseases as, for example, herpetic keratitis in rabbits and herpetic encephalitis in mice.
As used in this reference the term "effective unit dosage" or "effective unit dose" is denoted to mean a predetermined antiviral amount sufficient to be effective against the viral organisms in vivo. Pharmaceutically acceptable carriers are materials useful for the purpose of administering the medicament, and may be solid, liquid or gaseous materials, which are otherwise inert and medically acceptable and are compatible with the active ingredients.
These pharmaceutical compositions may be given parenterally, orally, used as a suppository or pessary, applied topically as an ointment, cream, aerosol, powder, or given as eye or nose drops etc., depending on whether the preparation is used to treat internal or external viral infections.
For internal infections the compositions are administered orally or parenterally at dose levels, calculated as the free base, of about 0.1 to 250 mg per kg, preferably 1.0 to 50 mg per kg, of mammal body weight, and are used in man in a unit dosage form, administered a few times daily in the amount of 1 to 250 mg per unit dose.
For oral administration, fine powders or granules many contain diluting, dispersing and/or surface active agents, and may be presented in a draught, in water or in a syrup; in capsules or sacnets in the dry state or in a non-aqueous solution or suspension, wherein suspending agents may be included; in tablets, wherein binders and lubricants may be included; or in a suspension in water or a syrup. Where desirable or necessary, flavoring, preserving, suspending, thickening or emulsifying agents may be included. Tablets and granules are preferred, and these may be coated.
For parenteral administration or for administration as drops, as for eye infections, the compounds may be presented in aqueous solution in a concentration of from about 0.1 to 10%, more preferably, 0.1 to 7%, most preferably 0.2% w/v. The solution may contain antioxidants, buffers, etc.
Alternatively for infections of the eye, or other external tissues e.g. mouth and skin the compositions are preferably applied to the infected part of the body of the patient as a topical ointment or cream. The compounds may be presented in an ointment, for instance, with a water soluble ointment base, or in a cream, for instance, with an oil in water cream base, in a concentration of from about 0.1 to 10%; preferably 0.1 to 7%, most preferably 1% w/v.